Targeted Therapy of Osteosarcoma Cancer: A Review

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, with a poor prognosis, especially in cases of metastatic or relapsed disease. Standard treatment approaches, including surgery and multi-agent chemotherapy, have reached a therapeutic plateau, with limited improvements in survival over the past several decades. Consequently, there is a critical need for novel therapeutic strategies that specifically target the molecular and biological underpinnings of osteosarcoma. Targeted therapies, which focus on key genetic alterations, dysregulated signaling pathways, and components of the tumor microenvironment, have emerged as a promising approach for improving outcomes in osteosarcoma patients. This review explores the current landscape of targeted therapy in osteosarcoma, emphasizing advances in the understanding of molecular targets and their clinical applications. Key pathways implicated in osteosarcoma pathogenesis, such as the PI۳K/Akt/mTOR, RAS/RAF/MEK/ERK, and VEGF signaling cascades, represent critical drivers of tumor growth, metastasis, and survival. Tyrosine kinase inhibitors (TKIs), which block aberrant signaling in these pathways, have shown potential in preclinical and early-phase clinical trials, although drug resistance remains a significant challenge. Combination therapies that target multiple signaling pathways simultaneously are being explored as a strategy to overcome resistance and enhance efficacy. In addition to kinase inhibitors, immune checkpoint inhibitors have gained attention as a promising approach in osteosarcoma therapy. These agents, which block inhibitory pathways in the immune system, aim to restore anti-tumor immune responses. While immune checkpoint inhibitors have demonstrated success in certain solid tumors, their efficacy in osteosarcoma has been more limited due to the immunosuppressive nature of the tumor microenvironment. Strategies that combine checkpoint inhibitors with agents that modulate the tumor microenvironment, such as CSF-۱R inhibitors and oncolytic viruses, are being investigated to enhance immune activation and improve therapeutic outcomes. Furthermore, epigenetic therapies and adoptive cell therapies, such as chimeric antigen receptor (CAR) T-cell therapy, represent novel approaches in osteosarcoma treatment. Epigenetic therapies aim to reverse aberrant gene expression patterns, while CAR T-cell therapy seeks to engineer immune cells to recognize and attack osteosarcoma cells. Although these therapies are still in the early stages of development, they hold significant potential for improving outcomes in osteosarcoma patients, particularly those with refractory disease. Despite the promising advances in targeted therapies, significant challenges remain, including drug resistance, tumor heterogeneity, and off-target toxicities. Future efforts must focus on overcoming these barriers through the development of more precise, combination-based approaches and expanding access to personalized medicine. Ultimately, targeted therapies hold the potential to revolutionize osteosarcoma treatment, offering new hope for improved survival and quality of life in patients.

کلیدواژه ها:

Osteosarcoma ، Targeted therapy ، Tyrosine kinase inhibitors (TKIs) ، Immunotherapy ، Tumor microenvironment